In chronic myeloid leukemia, which translocation is characteristic and what drug targets it?

• A. t(11;14) CCND1; alkylating agents
• B. t(9;22) BCR-ABL; targeted by tyrosine kinase inhibitors (e.g., imatinib)
• C. t(15;17) PML-RARA; all-trans retinoic acid
• D. t(8;14) MYC; CHOP

Answer: (B)

In chronic myeloid leukemia, the defining genetic change is the translocation between chromosomes 9 and 22 that forms the BCR-ABL fusion gene. This fusion protein has constitutive tyrosine kinase activity, which drives the unchecked proliferation of myeloid cells. Because the disease hinges on this specific kinase, treatment targets it directly with tyrosine kinase inhibitors such as imatinib. These drugs bind to the BCR-ABL kinase, blocking its signaling and controlling the leukemia. For context, the other translocations point to different diseases and therapies: t(11;14) involving CCND1 is characteristic of mantle cell lymphoma and isn’t treated by alkylating agents as a defining approach; t(15;17) PML-RARA is seen in acute promyelocytic leukemia and is treated with all-trans retinoic acid; and t(8;14) involving MYC occurs in Burkitt lymphoma and is typically approached with CHOP-based regimens.